The long-term objective of this research project is to study the roles of key coagulation system components in tumor growth and metastasis. Until recently, an in vivo model in which specific components of the clotting system could be reliably inhibited without affecting other components has not existed. The development of gene-targeted mouse lines with specific deficits in hemostatic factors has opened the door for just such studies. We propose to explore the biology of various in vivo cancer models in mice bearing specific hemostatic deficits. The goals will be to define the role of fibrinogen and platelets in tumor stroma formation and, hence, tumor growth; define the role of fibrinogen and platelets in tumor metastasis; and to define the role played by the combination of platelet activation, platelet interaction with fibrinogen, and fibrin polymer formation in tumor metastasis.